Ignite Creation Date:
2025-12-24 @ 5:56 PM
Ignite Modification Date:
2025-12-30 @ 9:58 AM
Study NCT ID:
NCT05212168
Status:
COMPLETED
Last Update Posted:
2025-11-05
First Post:
2022-01-25
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Norovirus Challenge Study
Sponsor:
Vaxart
Organization:
Study Overview
Official Title:
A Phase 2b Double-Blinded, Randomized, Placebo-Controlled, Human Norovirus GI.1 (Norwalk Virus Inoculum) Challenge Study Following Administration of an Oral, Single-dose Norovirus Vaccine Expressing GI.1 VP1 and dsRNA Adjuvant to Protect Against Norovirus Gastroenteritis (NVG) in Healthy Adult Volunteers
Status:
COMPLETED
Status Verified Date:
2025-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
G1-1 Challenge
Brief Summary:
This is a Phase 2b randomized, double-blind, placebo-controlled vaccination and challenge study to assess the protective efficacy of the Vaxart Norovirus vaccine (VXA-G1.1-NN). Healthy adults will be randomized in a 1:1 ratio to receive one oral dose of vaccine or placebo.
* Arm 1: VXA-G1.1-NN oral vaccine tablets \[1x1011 IU±0.5 log\]
* Arm 2: Placebo tablets similar in appearance and number to active vaccine tablets
Approximately 28 days post-vaccination, subjects will be admitted to an isolation ward and challenged with the NV GI.1 Norwalk challenge strain. After challenge, subjects will be monitored for signs and symptoms of acute gastroenteritis (AGE) from Day 29 to discharge. At 4 days post challenge (Day 33) asymptomatic subjects will be discharged from the isolation ward and will be followed in a series of outpatient visits and telephone calls. Symptomatic subjects may be kept in the isolation ward for up to an additional 3 days.
* Arm 1: VXA-G1.1-NN oral vaccine tablets \[1x1011 IU±0.5 log\]
* Arm 2: Placebo tablets similar in appearance and number to active vaccine tablets
Approximately 28 days post-vaccination, subjects will be admitted to an isolation ward and challenged with the NV GI.1 Norwalk challenge strain. After challenge, subjects will be monitored for signs and symptoms of acute gastroenteritis (AGE) from Day 29 to discharge. At 4 days post challenge (Day 33) asymptomatic subjects will be discharged from the isolation ward and will be followed in a series of outpatient visits and telephone calls. Symptomatic subjects may be kept in the isolation ward for up to an additional 3 days.
Detailed Description:
Study Population Healthy male and female adult volunteers age 18 to 49 years inclusive with blood type O or A and who are confirmed H type-1 antigen secretory positive Investigational Product
Active Vaccine:
* Norovirus GI.1 Norwalk VP1 Vaccine (VXA-G1.1-NN), an Oral E1/E3-Deleted Replication-Defective Recombinant Adenovirus serotype 5 with double-stranded ribonucleic acid (dsRNA) Adjuvant. The vaccine vector encodes for a full-length VP1 gene from Norwalk virus (NV). The adjuvant is a short hairpin RNA, expressed as a 21 nucleotide sequence (GAAACGA TATGGGCTGAATAC) as a tandem sequence in forward and reverse orientations separated by 6 nucleotides that comprise the loop of the RNA. The final drug product (DP) is formulated into enteric-coated tablet.
* Dose: 1x10E11 IU±0.5 log
Placebo Control:
• Oral tablets similar in appearance and number to active vaccine tablets Multiple tablets of study drug will be dispensed to allow delivery of the intended vaccine dose (1x10E11 IU). A matching number of placebo tablets will be dispensed to maintain the study blinding.
Viral Challenge Inoculum
* Norovirus GI.1 (Norwalk Virus Inoculum Lot 001-09NV, IND 14697)
* Dose: 1x10E6 Genomic Copies (GC). A dose which allows 50% - 65% infectivity in the healthy adult population (per NV infection rate observed in the GI.1 viral titration study
Study Hypothesis Norovirus vaccine (VXA-G1.1-NN) will protect against Norovirus Gastroenteritis (NVG) related to norovirus (NoV) infection in the challenge model
Approximately 120 subjects will be dosed in the vaccination phase to ensure at least 100 subjects (\~ 50 VXA-G1.1-NN vaccine and 50 placebo) are available to participate in the challenge phase. Approximately 28 days post-vaccination, subjects will be admitted to an isolation ward and challenged with the NV GI.1 Norwalk challenge strain. After challenge, subjects will be monitored for signs and symptoms of acute gastroenteritis (AGE) from Day 29 to discharge. NV illness lasts 2-4 days and is self-limited. At 4 days post challenge (Day 33) asymptomatic subjects will be discharged from the isolation ward and will be followed in a series of outpatient visits and telephone calls. Symptomatic subjects may be kept in the isolation ward for up to an additional 3 days.
The following study visits and remote contacts will be conducted during the study
Vaccination Phase:
* Pre-Screening Period (Days -90 to Screening) may be utilized for purposes of ascertaining subjects' H type-1 antigen secretory status and blood type
* Screening Period (Days -45 to -1)
* Day 1 Visit (Baseline assessments; day of randomization and vaccination)
* Day 8 Visit (safety and evaluation of immune response)
* Day 28 (evaluation of immune response; 1 day prior to challenge, start inpatient stay)
Challenge Phase:
* Day 29 (viral challenge, sequestration)
* Days 30 to 33 (sequestration - discharge; +3 days)
* Day 36 Visit (evaluation of immune response and safety assessment)
* Day 57 Visit (end of active period)
Safety Follow-Up:
* Day 120, Day 180, Day 240 and Day 300 (follow-up contact)
* Day 185 (follow-up phone call): Study completion
An independent Safety Monitoring Committee (SMC) will convene at pre-defined intervals during the norovirus challenge period, and also ad hoc as needed during the vaccination and challenge periods, to oversee the safety of the study.
Active Vaccine:
* Norovirus GI.1 Norwalk VP1 Vaccine (VXA-G1.1-NN), an Oral E1/E3-Deleted Replication-Defective Recombinant Adenovirus serotype 5 with double-stranded ribonucleic acid (dsRNA) Adjuvant. The vaccine vector encodes for a full-length VP1 gene from Norwalk virus (NV). The adjuvant is a short hairpin RNA, expressed as a 21 nucleotide sequence (GAAACGA TATGGGCTGAATAC) as a tandem sequence in forward and reverse orientations separated by 6 nucleotides that comprise the loop of the RNA. The final drug product (DP) is formulated into enteric-coated tablet.
* Dose: 1x10E11 IU±0.5 log
Placebo Control:
• Oral tablets similar in appearance and number to active vaccine tablets Multiple tablets of study drug will be dispensed to allow delivery of the intended vaccine dose (1x10E11 IU). A matching number of placebo tablets will be dispensed to maintain the study blinding.
Viral Challenge Inoculum
* Norovirus GI.1 (Norwalk Virus Inoculum Lot 001-09NV, IND 14697)
* Dose: 1x10E6 Genomic Copies (GC). A dose which allows 50% - 65% infectivity in the healthy adult population (per NV infection rate observed in the GI.1 viral titration study
Study Hypothesis Norovirus vaccine (VXA-G1.1-NN) will protect against Norovirus Gastroenteritis (NVG) related to norovirus (NoV) infection in the challenge model
Approximately 120 subjects will be dosed in the vaccination phase to ensure at least 100 subjects (\~ 50 VXA-G1.1-NN vaccine and 50 placebo) are available to participate in the challenge phase. Approximately 28 days post-vaccination, subjects will be admitted to an isolation ward and challenged with the NV GI.1 Norwalk challenge strain. After challenge, subjects will be monitored for signs and symptoms of acute gastroenteritis (AGE) from Day 29 to discharge. NV illness lasts 2-4 days and is self-limited. At 4 days post challenge (Day 33) asymptomatic subjects will be discharged from the isolation ward and will be followed in a series of outpatient visits and telephone calls. Symptomatic subjects may be kept in the isolation ward for up to an additional 3 days.
The following study visits and remote contacts will be conducted during the study
Vaccination Phase:
* Pre-Screening Period (Days -90 to Screening) may be utilized for purposes of ascertaining subjects' H type-1 antigen secretory status and blood type
* Screening Period (Days -45 to -1)
* Day 1 Visit (Baseline assessments; day of randomization and vaccination)
* Day 8 Visit (safety and evaluation of immune response)
* Day 28 (evaluation of immune response; 1 day prior to challenge, start inpatient stay)
Challenge Phase:
* Day 29 (viral challenge, sequestration)
* Days 30 to 33 (sequestration - discharge; +3 days)
* Day 36 Visit (evaluation of immune response and safety assessment)
* Day 57 Visit (end of active period)
Safety Follow-Up:
* Day 120, Day 180, Day 240 and Day 300 (follow-up contact)
* Day 185 (follow-up phone call): Study completion
An independent Safety Monitoring Committee (SMC) will convene at pre-defined intervals during the norovirus challenge period, and also ad hoc as needed during the vaccination and challenge periods, to oversee the safety of the study.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: